The inflammatory cellular infiltrates found in human gingival tissue are presumed to mediate the pathogenesis of periodontal disease. However, the nature of the host defense mechanisms involved in the destruction of gingival tissue and alveolar bone remain unclear. In vitro studies of dental plaque and microbial antigen-stimulated human peripheral blood lymphocytes have suggested roles for cellular and humoral responses as well as for immune complexes. These studies are only presumptive since they examined peripheral blood lymphocytes. This proposal seeks to define, in situ, then isolate and functionally characterize the immunological and nonspecific effector responses of lymphocytes present in periodontal lesion cellular infiltrates. The first experimental approach will be to characterize cellular infiltrates of periodontal lesions in situ by morphological, cytochemical, and immunopathological assessments. These studies will seek to define distinct features of inflammatory cellular infiltrates which correlate with independently assigned clinical disease categories - mild-gingivitis, severe gingivitis, and periodontitis. The second experimental approach will be to recover gingival lymphocytes, and other lymphocytes, and other inflammatory cells, from diseased gingiva, then characterize these cells using cell surface markers. These results should correlate with and extend the in situ findings as well as provide direction for the functional characterization studies. Thirdly, the in vitro effector responses presumed to be correlates of the in vivo disease will be assessed using isolated gingival lymphocytes which are effector cells actively involved in the pathogenesis of human periodontal disease. These functional evaluations will include immune lymphocyte blastogenesis, lymphokine production, cytotoxicity for gingival fibroblasts and antibody production. In addition, the regulatory roles of serum factors, immune complexes and certain lymphoid subpopulations on these gingival lymphocyte effector responses will also be investigated.